5 research outputs found

    A C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity.

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    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity

    Surgical Management of Ulcerative Colitis in Children and Adolescents: A Systematic Review from the APSA Outcomes and Evidence-Based Practice Committee.

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    INTRODUCTION: The incidence of ulcerative colitis (UC) is increasing. Roughly 20% of all patients with UC are diagnosed in childhood, and children typically present with more severe disease. Approximately 40% will undergo total colectomy within ten years of diagnosis. The objective of this study is to assess the available evidence regarding the surgical management of pediatric UC as determined by the consensus agreement of the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP). METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on surgical decision-making for children with UC. Questions focused on surgical timing, reconstruction, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of Bias was assessed using Methodological Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: A total of 69 studies were included for analysis. Most manuscripts contain level 3 or 4 evidence from single-center retrospective reports, leading to a grade D recommendation. MINORS assessment revealed a high risk of bias in most studies. J-pouch reconstruction may result in fewer daily stools than straight ileoanal anastomosis. There are no differences in complications based on the type of reconstruction. The timing of surgery should be individualized to patients and does not affect complications. Immunosuppressants do not appear to increase surgical site infection rates. Laparoscopic approaches result in longer operative times but shorter lengths of stay and fewer small bowel obstructions. Overall, complications are not different using an open or minimally invasive approach. CONCLUSIONS: There is currently low-level evidence related to certain aspects of surgical management for UC, including timing, reconstruction type, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. Multicenter, prospective studies are recommended to better answer these questions and ensure the best evidence-based care for our patients. LEVEL OF EVIDENCE: Level of evidence III. STUDY TYPE: Systematic review

    Evaluation and Management of Primary Spontaneous Pneumothorax in Adolescents and Young Adults: A Systematic Review From the APSA Outcomes & Evidence-Based Practice Committee.

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    INTRODUCTION: Controversy exists in the optimal management of adolescent and young adult primary spontaneous pneumothorax. The American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL, Elsevier Scopus, and Wiley Cochrane Central Register of Controlled Trials databases were queried for literature related to spontaneous pneumothorax between January 1, 1990, and December 31, 2020, addressing (1) initial management, (2) advanced imaging, (3) timing of surgery, (4) operative technique, (5) management of contralateral side, and (6) management of recurrence. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Seventy-nine manuscripts were included. Initial management of adolescent and young adult primary spontaneous pneumothorax should be guided by symptoms and can include observation, aspiration, or tube thoracostomy. There is no evidence of benefit for cross-sectional imaging. Patients with ongoing air leak may benefit from early operative intervention within 24-48 h. A video-assisted thoracoscopic surgery (VATS) approach with stapled blebectomy and pleural procedure should be considered. There is no evidence to support prophylactic management of the contralateral side. Recurrence after VATS can be treated with repeat VATS with intensification of pleural treatment. CONCLUSIONS: The management of adolescent and young adult primary spontaneous pneumothorax is varied. Best practices exist to optimize some aspects of care. Further prospective studies are needed to better determine optimal timing of operative intervention, the most effective operation, and management of recurrence after observation, tube thoracostomy, or operative intervention. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Systematic Review of Level 1-4 studies
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